Dynamics of Airway Macrophage Responses and Lung Function Changes after Ozone Exposure in Humans

Ozone is a ubiquitous ambient air pollutant known to cause lung injury and exacerbate pulmonary disease. While rodent studies suggest that macrophages contribute to both ozone-induced lung injury and subsequent repair, their specific roles in humans remain unclear. We hypothesized that recovery from ozone-induced lung injury in humans depends on a dynamic balance between macrophage subsets. To test this hypothesis, 44 healthy male and female adults (18-40 years old) were enrolled in a randomized, single-blind cross-over study involving paired 3 h exposures to ozone (200 ppb) and filtered air. Participants were evaluated 24, 48, or 72 h after each exposure, at which time induced sputum was collected for myeloid cell analysis. Pulmonary function testing was performed before and immediately after each exposure and repeated at the follow-up visit. Compared with filtered air, ozone exposure resulted in a significant increase in the percentage of monocytes at 24 h and monocyte-derived macrophages at 24-72 h, while neutrophil percentages decreased at 48-72 h. Immediately after ozone exposure, participants showed significant reductions in FEV₁, FVC, and the FEV₁/FVC ratio, along with increases in distal airway resistance measures (R5 and R10). These functional impairments were not evident at 24-72 h. Improvements in large airway lung function from 24-72 h post-ozone exposure correlated with a higher airway monocyte-derived macrophage-to-neutrophil ratio, while improvement in R5 associated with a higher monocyte-derived macrophage-to-monocyte ratio. These findings provide new insight into the temporal sequence of human airway macrophage responses following ozone-induced lung injury and highlight coordinated macrophage dynamics that may contribute to recovery.